PGF(2alpha) is one of the major prostanoids produced by the kidney. The cellular effects of PGF(2alpha) are mediated by a G protein-coupled transmembrane receptor designated the FP receptor. Both in situ hybridization and beta-galactosidase knocked into the endogenous FP locus were used to determine the cellular distribution of the mouse FP receptor. Specific labeling was detected in the kidney, ovary, and uterus. Abundant FP expression in ovarian follicles and uterus is consistent with previous reports of failed parturition in FP-/- mice. In the kidney, coexpression of the mFP mRNA with the thiazide-sensitive cotransporter defined its expression in the distal convoluted tubule (DCT). FP receptor was also present in aquaporin-2-positive cortical collecting ducts (CCD). No FP mRNA was detected in glomeruli, proximal tubules, or thick ascending limbs. Intrarenal expression of the FP receptor in the DCT and CCD suggests an important role for the FP receptor regulating water and solute transport in these segments of the nephron.